Monomer/Dimer Transition of the Caspase-Recruitment Domain of Human Nod1

Journal Article · Tue Jan 01 04:00:00 EST 2008 · Biochemistry

DOI:https://doi.org/10.1021/bi7016602· OSTI ID:959822

Srimathi, T; Robbins, S; Dubas, R; Hasegawa, M; Inohara, N; Park, Y

Nod1 is an essential cytoplasmic sensor for bacterial peptidoglycans in the innate immune system. The caspase-recruitment domain of Nod1 (Nod1{_}CARD) is indispensable for recruiting a downstream kinase, receptor-interacting protein 2 (RIP2), that activates nuclear factor-?B (NF-?B). The crystal structure of human Nod1{_}CARD at 1.9 Angstroms resolution reveals a novel homodimeric conformation. Our structural and biochemical analysis shows that the homodimerization of Nod1{_}CARD is achieved by swapping the H6 helices at the carboxy termini and stabilized by forming an interchain disulfide bond between the Cys39 residues of the two monomers in solution and in the crystal. In addition, we present experimental evidence for a pH-sensitive conformational change of Nod1{_}CARD. Our results suggest that the pH-sensitive monomer/dimer transition is a unique molecular property of Nod1{_}CARD.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 959822
• Report Number(s): BNL--82808-2009-JA
• Journal Information: Biochemistry, Journal Name: Biochemistry Vol. 47; ISSN 0006-2960; ISSN BICHAW
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
CONFORMATIONAL CHANGES
CRYSTAL STRUCTURE
DISULFIDES
MONOMERS
PROTEINS
RESIDUES
RESOLUTION
national synchrotron light source